Cancer is a disease of major impact in world health. In 1999, over 1 million people living in the United States alone, had been diagnosed with cancer. Furthermore, because of the aging of the population, this number is expected to double over the next fifty years. Therefore, there is a need to identify new agents for treating cancer. Furthermore, since effective treatment of cancer requires early and accurate diagnosis, there is a need for new methods for detecting and diagnosing cancer.
It is known that cancer is a genetic disorder. That is, an individual's particular genetic makeup influences whether and when the individual will develop cancer. Recent studies have focused on identifying the changes at a molecular level, that lead to cancer, in order to identify new diagnostics and treatment modalities. Studies of cancer predisposition have focused on genes in which mutations have a major impact on cancer formation and/or progression, called high penetrance genes. However, such genes although relatively easy to identify, account for only a small portion of cancer risk. The majority of cancer risk is associated with more difficult to find genes, known as low penetrance genes. Therefore, there is a need to identify low penetrance genes.
The human genome project has provided a tremendous amount of information regarding the nucleotide sequence of the human genome. However, this information was generated from analysis of the genomes of only a few individuals. Therefore, it does not provide sufficient information regarding the variability of the genome among individuals to allow an identification of differences between individuals that influence cancer risk. Therefore, there remains a need to identify differences between genomes of individuals which are responsible for the variability in cancer predisposition among individuals.
In addition to the characterization of human polymorphisms, identification of low penetrance tumor genes can be facilitated by identification of these genes in non-human species. Genomes of organisms, including mammals, are related, mainly because they arose from a common ancestor, and because basic cellular processes are conserved. Certain mammals, such as mice, lend themselves well to genetic studies in which the results of controlled animal crosses can be used to identify important regions of the genome for diseases such as cancer. However, there remains a need to develop methods which utilize genetics of non-human mammals to assist in the identification of regions of the human genome that are important for determining an individual's cancer disposition.